Aduro’s (NASDAQ:ADRO) CRS-207 is the second pancreatic cancer vaccine to crash and burn this month, and the fourth drug candidate to fail in the disease this year. But perhaps most worrying is the fact that the control arm outperformed the main treatment arm – a phenomenon that was also seen last week with NewLink Genetics’ (NASDAQ:NLNK) vaccine algenpantucel-L.
This raises the question of whether cancer vaccines might be harmful rather than just ineffective. Two studies do not make a trend, but it is something that will be closely watched in future cancer vaccine trials – and could be another hurdle for an already troubled field (Therapy focus – Testing times for cancer vaccines, May 12, 2016).
Aduro had been hoping to show an overall survival benefit with CRS-207 plus GVAX Pancreas, another cancer vaccine, in the Eclipse phase IIb study in third-line pancreatic cancer – but actually found decreased survival in this arm.
Overall survival was increased in the CRS-207 monotherapy arm versus the control arm. Patients in the latter were scheduled to receive single-agent chemotherapy and this group saw a “disproportionately high dropout rate” that could have confounded results, Aduro believes.
One drawback of the trial was the inability to blind patients to what treatment they would be receiving, explained chief executive Steve Isaacs on a conference call to discuss the results – meaning that control patients, disappointed at not being in the immunotherapy arm, dropped out before receiving their first chemotherapy session and ended up getting more aggressive combination treatment including chemotherapies, immunotherapies and targeted therapies.
This made the trial results “largely uninterpretable” according to Leerink analysts.
Nonetheless, Aduro does not plan on taking CRS-207 plus GVAX Pancreas into a phase III trial. “The jury is out on what effect GVAX has – it appears not to add to the party but it’s not clear if it has a negative effect,” said Mr Isaacs. The company is currently analysing this.
Next up for Aduro is the Stellar study, also of CRS-207, but with some differences: as well as GVAX Pancreas it also incorporates Bristol-Myers Squibb’s checkpoint inhibitor Opdivo, and is enrolling second-line pancreatic cancer patients. Interim data are expected in the second half.
The Leerink analysts have written off CRS-207’s chances in pancreatic cancer, not good news for an area that has seen multiple failures already this year (NewLink’s pancreatic cancer candidate fails to Impress, May 10, 2016).
Aduro could still salvage a result with CRS-207 in mesothelioma, where the analysts assign a 40% probability of success. However, the group has now put on hold plans to start a phase III trial this year while data from an ongoing phase Ib study mature – which could push back a potential launch by two years to 2021.
It is possible that Aduro could combine CRS-207 with a checkpoint inhibitor in mesothelioma; the phase III trial design is expected to be finalized by the end of the year.
Aduro’s share price closed down 17% yesterday, but it is not game over for the company. Roth analysts pointed to “the depth of the pipeline…strength of the balance sheet and pharma partners in hand”.
The focus now shifts to other pipeline assets including ADU-S100, based on another of the company’s platforms, Sting (Pre-IPO Sting gives Novartis a stake in Aduro, March 30, 2015). Aduro’s partner Novartis last week began a phase I trial in patients with solid tumors or lymphoma, with data expected in the second half of 2017.
With around $400m in cash at the end of Q1, Aduro is well financed to see its next catalysts through. It just looks like it will need more time to get its first product to market.